In the prior art, various types of apparatus have been proposed for noninvasively measuring the concentration of blood sugar in a subject.
In Japan Laid-Open Patent Publication No. 5-508336, for example, there is proposed a method for measuring the concentration of blood sugar in a human subject by using clear infrared radiation. According to this method, the subject is irradiated with near infrared radiation at wavelengths of 600 nm to 1100 nm, and the blood sugar concentration is obtained by analyzing specific wavelength components of the light passed through the subject.
While near infrared light has the advantage that it is suitable for analysis because, compared with infrared light, near infrared light is less strongly absorbed by water and therefore easily passes through aqueous solutions and living bodies, the disadvantages are that it is difficult to extract information concerning individual components because the absorption peaks of various components overlap in a complicated manner compared with infrared light, and that the absorption peak wavelength can easily change widely with temperature; with these and other disadvantages, the near infrared method has not yet been implemented commercially.
As opposed to that, Japan Laid-Open Patent Publication No. 11-178799 proposes a method for measuring glucose, water content, etc. in a superficial tissue of a living body by using near infrared radiation. According to this first prior art method, the superficial tissue of a living body, with a portion thereof raised, is placed in a single groove formed in a flat member; in this condition, near infrared radiation is emitted from an optical fiber bundle placed on one side of the raised portion, and is received by an optical fiber bundle placed on the opposite side of the raised portion. Then, a portion of the light diffusely reflected at the superficial tissue is detected and its spectrum analyzed, to obtain biological information, in particular, glucose, water content, etc. of the dermis tissue.
As a prior art example using mid-infrared radiation, there is proposed, for example, in Japan Laid-Open Patent Publication No. 9-11343, a method that uses an attenuated total reflection (hereinafter abbreviated ATR) measuring apparatus to measure specific constituents of a subject, especially, a living body.
A schematic diagram illustrating this method is shown in FIG. 11. As shown, a transparent ATR prism 20 having a pair of reflecting surfaces being parallel to each other on opposite sides thereof is placed in intimate contact with a lip mucosa 21 to measure the concentration of blood sugar. According to this method, the ATR prism is held in a mouth between the upper and lower lips, and the light emerging from the ATR prism 20 after undergoing attenuated total reflection at the interfaces between the lip mucosa 21 and the respective reflecting surfaces of the prism 20 is analyzed.
In BEME, vol. 5, No. 8 (Japanese Society of Medical Electronics and Biological Engineering, 1991), there is proposed a method in which, after an ATR prism formed from a ZnSe optical crystal or the like is placed in intimate contact with a lip mucosa, laser light at wavelengths of 9 to 11 microns is introduced into the prism and caused to undergo multiple reflections within the prism, and the absorbed light is analyzed to measure sugar blood and blood ethanol concentrations. According to this method, blood sugar and blood ethanol concentrations can be measured noninvasively in real time.
These methods use an evanescent wave (so-called seeping light) for quantitative analysis. As shown in FIG. 11, the light traveling through the prism 20 is reflected after its lightly penetrates into the lip mucosa 21. As a result, the light penetrating into the lip is affected by various constituents in the body fluid existing there. Therefore, by measuring the amount of reflected light, changes in the reflectance, absorptance, etc. of the body fluid can be detected, and each component in the body fluid can thus be obtained.
There is also proposed Fourier transform Raman spectroscopy that uses a laser light source such as an argon laser with an oscillation wavelength of 500 nm, a YAG laser with an oscillation wavelength of 1060 nm, or a semiconductor laser with an oscillation wavelength of 880 nm, irradiates a living tissue with the laser light emitted from the light source, and obtains biological information by detecting the light scattered within the living tissue (Raman scattered light) and by analyzing the spectrum of the detected Raman scattered light. According to this method, since the Raman scattered light has wavelengths characteristic of each individual kind of substance in the living tissue, the kinds of substances in the living tissue and their concentrations can be calculated by analyzing the spectrum of the Raman scattered light.
However, the prior art noninvasive blood sugar measuring apparatus described above have had the following problems.
The first prior art method has had the problem that if the optical fiber at the incident side and the optical fiber at the receiving side are not placed correctly opposite each other, the loss of light within the living tissue increases and the intensity of diffusely reflected light to be received decreases; furthermore, since the light penetrates deeply into the living tissue, there has been the problem that various diffusely reflected lights differing in optical path length, containing information not only on epidermis and dermis but also on deeper portions of the living tissue such as subcutaneous tissue, are detected.
Accordingly, when the target to be measured is skin tissue, it has been difficult to extract and measure biological information only on the superficial tissue of a living body, such as the epidermis about 100 to 200 microns thick and the underlying dermis about 500 to 1000 microns thick in the case of mucous tissue also, it has been difficult to measure biological information only on the superficial tissue such as epitheliums and lamina propria mucosae.
Furthermore, when measuring components of light traveling in straight lines through a living tissue by using optical fibers placed opposite each other, a mechanical raising means i's needed to vertically raise the surface of the living tissue, which not only imposes an extra strain on the living tissue but may cause a pain, and further, it has been difficult to place the end face of each optical fiber in intimate contact with the superficial tissue of the living body stably with constant pressure.
Moreover, since very thin optical fibers need to be brought close to the epidermic layer of the living body in order to precisely place the optical fiber bundles in intimate contact with the living body, the apparatus is complex in construction and takes a cumbersome procedure to assemble, and besides, it has been difficult to form a large number of grooves.
Though a single groove formed in a flat member is placed in intimate contact with the living body in order to raise a portion of the living body, it has been difficult to sufficiently raise the portion of the living body.
Furthermore, since it is difficult to increase the total area of the end face of the optical fibers, it has been difficult to increase the intensity of diffusely reflected light used for measurement.
On the other hand, the second and third prior art methods have had the following problems.
It is known that the depth, d, to which the evanescent wave penetrates is roughly determined by the following equation (1).             [              MATHEMATICAL        ⁢                                   ⁢        1            ]        ⁢                                                                               ⁢                                           ⁢                      d            =                          λ                              2                ⁢                                                                   ⁢                π                ×                                                                                                    sin                        2                                            ⁢                                                                                           ⁢                      θ                                        -                                                                  (                                                                              n                            2                                                                                n                            1                                                                          )                                            2                                                                                                                                (          1          )                    
Here, λ is the wavelength of light, θ is the angle of incidence, n1 is the refractive index of the crystal, and n2 is the refractive index of the medium placed in contact with the crystal.
For example, when the wavelength of light is 10 microns, the ATR prism is formed from a ZnSe crystal (refractive index of about 2.41), the angle of incidence is 45 degrees, and the surrounding medium is water (refractive index: about 1.0), then the penetration depth, d, can be calculated as d=2.8 microns from the equation (1). If the refractive index of the surrounding medium changes, the seeping depth also changes, as can be seen from the equation (1), but in any case, the change is a few microns at most, which means that information concerning the surface of the living body and its neighborhood can be obtained using the above-described prior ART measuring apparatus.
However, in this case, information concerning the portions of the living body deeper than a few microns is difficult to obtain; in particular, if there is an external disturbing layer such as an impurity or saliva between the apparatus and the analyte, the depth to which the signal penetrates into the living body changes, causing the signal to change.
Accordingly, in the above-described prior art methods which require the ATR prism be pressed against a lip, the contact between the lip and the surface of the prism is not stable and it is difficult to make measurements with high accuracy. Further, if saliva is present between the prism and the lip, for example, the measured value will be greatly affected by the presence of the saliva.
The ATR prism used for the above purpose is formed from an optical crystal such as ZnSe, ZnS, and KrS. Since these materials are very soft and therefore require great care in handling and cleaning, it is difficult to measure many subjects in succession.
In the fourth prior art method, on the other hand, since the laser light is directed into the living tissue, the laser light entering the living tissue is mostly absorbed in the living tissue. If Raman scattered light of the intensity necessary to detect biological information is to be obtained, laser light of great intensity must be shone on the living tissue, but this has involved the problem that a burn may be caused because the laser light is absorbed in the living tissue.